A graft-versus-host disease-like pattern in capecitabine-induced gastrointestinal injury
Capecitabine is a commonly used oral chemotherapeutic agent with well-known gastrointestinal side effects. However, its histopathologic changes have not been studied comprehensively. The authors conducted a study in which they described a large case series (eight patients) characterizing the histopathology of capecitabine-induced GI injury. All patients were adults (median age, 64.5 years; range, 61–76 years) and there was gender parity. Patients were receiving treatment for malignancies of the colorectum (n=5), breast (n=1), pancreas (n=1), and appendix (n=1). All had GI symptoms, including seven with diarrhea and abdominal pain and one with melena. Five of the eight showed graft-versus-host disease (GVHD)-like histologic changes in small intestinal or colonic biopsies characterized by crypt disarray and dropout, crypt atrophy, dilated crypts lined by attenuated epithelium, and increased crypt apoptosis. Neuroendocrine cell aggregates were present in four of five patients. Four of five showed patchy prominence of lamina propria eosinophils. One patient receiving concomitant radiation therapy had a small intestinal biopsy showing regenerative changes. Two patients had histologically unremarkable biopsies. On follow-up, capecitabine was discontinued or the dose was reduced in all patients. Three of five patients with a GVHD-like pattern had clinical improvement, and two died shortly after biopsy. The patient with regenerative changes also had the radiation dose reduced and improved clinically. Two with unremarkable biopsies improved symptomatically. In summary, capecitabine-related GI injury shows a GVHD-like pattern. Knowledge of this is important to confirm the diagnosis, as patients typically improve with reduced doses or discontinuation of the drug.
Ojukwu K, Cox BK, Larson BK, et al. Capecitabine-induced gastrointestinal injury shows a graft-versus-host disease (GVHD)-like pattern. Am J Surg Pathol. 2023;47(10):1160–1167.
Correspondence: Dr. Danielle A. Hutchings at danielle.hutchings@cshs.org
Significance of FIGO grading in MSI-H and POLE-mutant endometrioid endometrial carcinoma
With the advancement of diagnostic molecular technology and molecular classification of endometrial endometrioid carcinoma, it remains to be seen whether conventional International Federation of Gynecology and Obstetrics (FIGO) grading is still clinically significant for certain molecular subtypes of the cancer. The authors conducted a study in which they explored the clinical significance of FIGO grading in microsatellite instability-high (MSI-H) and POLE-mutant endometrial endometrioid carcinomas (EECs). The analysis included 162 cases of MSI-H EEC and 50 cases of POLE-mutant EEC. Significant differences in tumor mutation burden (TMB), progression-free survival, and disease-specific survival were noted between the MSI-H and POLE-mutant cohorts. The MSI-H cohort had statistically significant differences in TMB and stage at presentation across FIGO grades but not survival. The POLE-mutant cohort had significantly greater TMB with increasing FIGO grade but no significant differences in stage or survival. In both cohorts, log-rank survival analysis showed no statistically significant difference in progression-free and disease-specific survival across FIGO grades. Similar findings were found when using a binary grading system. The authors concluded that molecular profile overrides FIGO grade in predicting the biological behavior of EECs in MSI-H and POLE-mutant EEC.
Kertowidjojo E, Momeni-Boroujeni A, Rios-Doria E, et al. The significance of International Federation of Gynecology and Obstetrics grading in microsatellite instability-high and POLE-mutant endometrioid endometrial carcinoma. Mod Pathol. 2023;36(9). doi:10.1016/j.modpat.2023.100234
Correspondence: Dr. E. Kertowidjojo at ekertowi@bsduchicago.edu